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Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

ABSTRACT: The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metastasis. Overexpression of BLACAT2 promoted bladder cancer-associated lymphangiogenesis and lymphatic metastasis in both cultured bladder cancer cell lines and mouse models. Furthermore, we demonstrate that BLACAT2 epigenetically upregulated VEGF-C expression by directly associating with WDR5, a core subunit of human H3K4 methyltransferase complexes. Importantly, administration of an anti-VEGF-C antibody inhibited LN metastasis in BLACAT2-overexpressing bladder cancer. Taken together, these findings uncover a molecular mechanism in the lymphatic metastasis of bladder cancer and indicate that BLACAT2 may represent a target for clinical intervention in LN-metastatic bladder cancer.

SUBMITTER: He W

PROVIDER: S-EPMC5785244 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

He Wang W Zhong Guangzheng G Jiang Ning N Wang Bo B Fan Xinxiang X Chen Changhao C Chen Xu X Huang Jian J Lin Tianxin T

The Journal of clinical investigation 20180122 2

The prognosis for bladder cancer patients with lymph node (LN) metastasis is dismal and only minimally improved by current treatment modalities. Elucidation of the molecular mechanisms that underlie LN metastasis may provide clinical therapeutic strategies for LN-metastatic bladder cancer. Here, we report that a long noncoding RNA LINC00958, which we have termed bladder cancer-associated transcript 2 (BLACAT2), was markedly upregulated in LN-metastatic bladder cancer and correlated with LN metas ...[more]

PMID: 29355840

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Project description:ObjectiveIn this study, we aimed to clarify the effects of long noncoding ribonucleic acid prostrate androgen-regulated transcript-1 on bladder cancer cell proliferation and apoptosis.MethodsMicroarrays were implemented to investigate the long noncoding ribonucleic acid expression profiles in bladder cancer tissue (N = 9) and in noncancer bladder tissue (N = 5). Relative prostrate androgen-regulated transcript-1 expression levels in tissue samples or cell lines were detected by real-time quantitative reverse transcription-polymerase chain reaction. Prostrate androgen-regulated transcript-1 expression was enhanced by the transfection of pcDNA3.1-prostrate androgen-regulated transcript-1 and downregulated by the infection with pcMV-sh prostrate androgen-regulated transcript-1. Additionally, cell proliferation and apoptosis were measured by the cell counting kit-8 assay and flow cytometry, respectively. Cell invasion was determined by a Transwell assay.ResultsProstrate androgen-regulated transcript-1 expression was upregulated in bladder cancer tissues compared to adjacent nontumor tissues. Furthermore, prostrate androgen-regulated transcript-1 levels were successfully upregulated by pcDNA3.1-prostrate androgen-regulated transcript-1 and depleted by pCMV-sh prostrate androgen-regulated transcript-1 in bladder cancer cell lines (5637, T24). Enhanced prostrate androgen-regulated transcript-1 expression promoted cell proliferation and invasion and inhibited cell apoptosis. However, knockdown of prostrate androgen-regulated transcript-1 expression inhibited cell proliferation and invasion and induced cell apoptosis.ConclusionIn summary, these data suggest that the knockdown of prostrate androgen-regulated transcript-1 represents a tumor suppressor player in bladder cancer and contributes to the inhibition of tumor proliferation, the promotion of cell apoptosis, and the suppression of cell invasion. Prostrate androgen-regulated transcript-1 may function as a new prognostic biomarker and as a feasible therapeutic target for patients with bladder cancer.

Dataset Information

Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

Publications

Long noncoding RNA BLACAT2 promotes bladder cancer-associated lymphangiogenesis and lymphatic metastasis.

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